Engineered ILCs with CAR and IL-15 for Solid Tumor Therapy

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Solution Overview

Problem

Current cancer therapies, particularly those involving conventional CD8+ T cells, face challenges such as exhaustion, poor tissue infiltration, and the need for prior antigen knowledge, limiting their effectiveness in treating solid cancers.

Innovation Solution

The development of engineered cytotoxic innate lymphoid cells (ILCs) equipped with non-endogenous expression vectors encoding IL-15 or STAT5B and chimeric antigen receptors (CARs) that bind to tumor antigens, allowing for targeted immunotherapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CD8+ T cells are used for cancer therapy, then antigen-specific immunity is achieved, but cell exhaustion and poor tissue infiltration occur

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidcell functionality duration

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent combines the antigen-specific targeting capability of CAR-T cells with the tissue infiltration and cytotoxic properties of innate lymphoid cells (ILCs) to create a hybrid cell type that overcomes the exhaustion and limited durability of conventional CD8+ T cells while maintaining target specificity

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The engineered ILCs represent a composite cellular construct that integrates features from different immune cell types (T cell antigen recognition + NK cell cytotoxicity and tissue infiltration) to achieve superior therapeutic performance with sustained functionality

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If conventional T cell-based therapies are used, then antigen-specific targeting is achieved, but prior antigen knowledge is required

Engineering Contradiction:

Improvetargeting precisionVSAvoidtherapy development complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent creates a universal CAR-ILC platform that can be applied across multiple cancer types by simply changing the CAR antigen specificity, eliminating the need for extensive antigen discovery and validation required for conventional T cell therapies while maintaining precise target engagement

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Strength

If engineered ILCs with IL-15 or STAT5B are used, then cytotoxicity is enhanced, but cell composition complexity increases

Engineering Contradiction:

Improvecytotoxic capabilityVSAvoidcell engineering complexity

Core Design Contradiction:

StrengthVSDevice complexity

Solution Approach 1:

The patent modifies key molecular parameters within the ILCs by introducing IL-15 or STAT5B to alter cellular metabolism, enhance cytotoxic molecule expression, and improve persistence, thereby boosting cytotoxic capability through controlled biochemical parameter changes rather than structural complexity

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250154463A1Compositions including cytotoxic innate lymphoid cells and uses thereof

Publication Date: 2025.05.15 MEMORIAL HOSPITAL FOR CANCER & ALLIED DISEASES

AI summary

Disclosed herein are compositions including cytotoxic innate lymphoid cells (ILCs), methods for preparing ILCs for adoptive cell therapy, and methods of using ILCs to treat cancer.